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CONFIRMED FOLATE DEFICIENCIES - PLEASE POST HERE

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Freddd, Jan 10, 2012.

  1. Freddd

    Freddd Senior Member

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    I have seen a number of people confiming in themselves various forms of folate deficiencies by elliminating folic acid, folinic acid, NAC, glutathione, whey and maybe some other things and trying Metafolin. I am right now working on a questiionaire for detecting these deficiencies. I would like anybody willing to post the specific symptoms that the see changing with the Metafolin. For me that ranges from the very fast changing ones; IBS, angular cheilitis (sores ar corner of mouth), nausea, malaise, increase allergy, asthma, inflammation, depression, irritability, cold feet, edema, lower potassium when folate deficiency corrected, to lower MCV, lower MCH, increased platelet count over a longer period. The more exact and specific you can be, the more hlepful this will be. Also please mention which items you found to be a problem for you. Thankyou.

  2. Nielk

    Nielk

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    Hi Fredd,

    Is there a test to see what one's folate level is?
  3. gu3vara

    gu3vara Senior Member

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    I started eliminating all folic acid and folinic supplements, I'll report on my progress. Didn't see much changes on the SMP in three months unfortunately, maybe it's too soon.
  4. Freddd

    Freddd Senior Member

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    Hi Nielk,

    There are a number of tests possible at various costs. However, they may or may not show anything. General serum and cellular folate levels might be quite high in paradoxical folate deficiency because the folates present can't be depleated by being used. In the glutathione induced folate deficiency serum folate might be high while cellular methylfolate levels might be low. However, not existing in a vacuuim,tI have no idea about the other folates that might not be usable by the person. A Metafolin trial will tell you for $12.40 absolutely whether it makes a noticable difference or not, sometimes in less than 2 hours to a few days. However, hundreds of dollars worth of tests will not tell you whether Metafolin will make that difference or not. Give them another 65 years to understand an perfect the tests and interpretation of tests. They still don't have it right on mb12 or adb12 after b12 was identified on 64 years ago. I'm the same age as b12. Mb12 has only been available for 14 years. Metafolin has only been available for 5 years or so. They might know enough about these to use them effectively for my great great grandchildren. My first and only grandchild is only 2 yeras old. Her grandchild might be able to benefit. The only test that will give you the answers these days is a trial. Research on B12 will tell you that the tests are worthless and only a trial will tell you if and how much you can benfit, and they are 60 years ahead of the Metafolin curve.
  5. Freddd

    Freddd Senior Member

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    Hi Gu3vara,

    I don't know. Three months sure seems like a long time not to be able to tell anything in all this. I knew 15 minutes after taking mb12 that my life was CHANGED. In one day methylation and atp had started up. In 10 days my sore buring bladder was almost normal after more than a decade or more of burning pain. In 10 days my "beef-red" burning tongue was no longer red or burning after a decade or more of burning. In 10 days chronic nausea and daily vomitting had stopped completely. In ten days I had complete cessation of nightime acid eruptions multiple times a night up my throat. In 3 months I had the complete removal of 50 symptoms or so and redcuction of another 100 and others shifting around. There was no doubt I was healing. In 9 months I started reducing or quitting most of the medications I had been on.
  6. Rosebud Dairy

    Rosebud Dairy Senior Member

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    I still haven't sorted it all out, but i have found some of the following --

    crashing badly if my 3 basics (methylfolate, methylcobalamin, potassium --food based) are stopped for more than a couple of days

    inflammation
    itching,
    possible IBS flares
    depression

    more will follow
  7. Athene

    Athene Never give up

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    Hi Freddd,

    I took folinic acid (Kirkman brand) and had the following symptoms, which built up steadily over a three week period until I stopped taking the tablets. I tried this on two separate occasions with a "detox" break in between:

    - Muscular weakness, which I think was caused by weakening of the nerve signals
    - nausea and overpowering sense of being poisoned: the only way I can describe it is that I felt I was about to vomit from every part of my body
    - imparment of co-ordination (tripping on stairs, twitching, dropping things, bumping into doorframes etc in broad daylight!)
    - impairment of speed of reactions: most noticeable when driving as I became fairly incompetent to drive, it was as if I were having split second mental "blanks", combined with the fact that I was not fully aware of where I was putting my own body parts, so I would think I had put the car in 3rd gear when actually it was back in first, for example, and then my foot would have a spasm on the pedals etc.
    - headaches
    - slight worsening of the usual gut problems, which you could probably describe as IBS

    The main thing though, was the incredible weakness and just feeling poisoned. I felt as if I had been kissed by a Dementor.
  8. Freddd

    Freddd Senior Member

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    Hi Athene,

    For me those things come if it becomes severe and prolonged, I don't get them the first few days now that I have learned to spot onset rapidly. Thankyou. Don't tease the Dementors. They don't play well with others.
  9. Jenny

    Jenny Senior Member

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    I started taking metafolin 2 months ago (mid Nov, 800 mcg a day). I also started Perrin lymph drainage massage nearly 3 months ago (mid Oct). There was no change until early Dec, when I was a bit worse for 3 weeks - more flu-like symptoms, more painful lymph nodes, more pain generally. My Perrin osteopath says getting worse in the first few months with the massage treatment is a common pattern, so on balance I put my worse state down to that treatment rather than the metafolin.

    I'm now more or less back to my 'normal' state for the time of year - mostly housebound, have to rest most of the day, a bit fluey and achey, a bit dizzy, headaches, a bit of pain in joints.

    I certainly didn't have any immediate effect from the metafolin.

    Jenny

    (I'm heterozygous for one MTHFR mutation and homozygous for another (C677T)).
  10. anniekim

    anniekim Senior Member

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    Hi Fredd,

    Sorry I am a bit confused. How do people determine they have folate deficiencies by stopping things such as nac, whey and taking metafolin?

    So when you say you want people to list symptoms they see changing you mean these symptoms now resolve once stopping the nac, whey etc and starting the metafolin, not start up, and thus indicate a masked folate deficiency? Many thanks
  11. Athene

    Athene Never give up

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    Hi Freddd,
    I stopped my vitamin B complex, which contained 400 mcg of folic acid, a couple of days ago. I should have checked and stopped it sooner, I do wish my brain worked a bit better.
    I've been taking it for ages, so that would mean that my Kirkman folinic acid dosage was on top of a permanent baseline level of "problem". I wonder if that could be why I got these symptoms rapidly and very severely? All the symptoms you have listed are things I live with pretty much all the time (apart from angular cheilitis which I have very rarely had). I'll see how things go and report back.

    Meanwhile, what is the problem with NAC? What does that do with regard to the folate problem?
    I have been taking that for about a month to help with Chlamydia pneumonia. It gets rid of a lot of the rotten symptoms of that infection (chronic sinusitis and laryngitis with sore throat and losing voice, tightness of breath like asthma, frequent headaches etc.). I'd say I generally feel improved since I started taking that.
  12. richvank

    richvank Senior Member

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    Hi, Athene.

    For what it's worth, I think that the problems with folic acid, folinic acid and glutathione (including supplements that help to build glutathione, such as NAC and whey protein) that some people experience are all separate issues. While Freddd reports having all of them, I don't believe that they necessarily go together in everyone who has one or another of them.

    My current working hypothesis for these is as follows:

    1. The problems with folic acid could be due to a person having inherited a slow form of the DHFR enzyme, so that they are not able to convert folic acid to tetrahydrofolate at as high a rate as normal. It has been published that people vary by a factor of five (500%) in their ability to do this. If folic acid is not converted, it enters the blood stream and competes with active forms of folate for entry into the cells. This would lower the availability of 5-methyl tetrahydrofolate in the cells, which would produce a partial methylation cycle block. Another way that folic acid could cause problems is that this conversion requires NADPH, which Dr. Cheney has found to be low in many of his ME/CFS patients. If this reaction lowers NADPH further, it will not be available to support other reactions in the methylation cycle and the folate metabolism, as well as glutathione reductase. This would cause problems in all those parts of the metabolism.

    2. The problems with folinic acid could be due to a polymorphism in the MTHFS (not to be confused with MTHFR) enzyme. I suspect that Freddd has this mutation. This is the only enzyme that can convert folinic acid to another form of folate, from which it can be converted to yet others. If folinic acid builds up, it has been published that it will inhibit the SHMT reaction, and that will inhibit the production of 5-methyl tetrahydrofolate, which is the one needed by methionine synthase in the methylation cycle. It will also inhibit the formation of new RNA and DNA, for the production of new cells. This especially impacts the production of blood cells, cells lining the gut, and cells of the hair follicles, thus causing problems there especially.

    3. The problems with glutathione and associated substances are likely due to an inherited mutation in the CblC complementation group (coded by the MMACHC gene), which is part of the B12 processing pathway inside the cells. If certain mutations are present in this gene, the result will be that glutathione will bind B12 as glutathionylcobalamin, and the cells will not be able to make use of it. This will then cause a partial methylation cycle block and a lowering of the feeding of fuel to the Krebs cycle in the mitochondria, lowering the ATP production of the cells. I think that Freddd has this one, too. Associated with this type of mutation is also an inability to use cyanocobalamin or hydroxocobalamin as one's B12 source, because the Cblc complementation group is responsible for preparing these for conversion to the coenzyme forms of B12 (methyl B12 and adenosyl B12). People who have this type of mutation, which I think Freddd has, need to put large amounts of these two coenzyme B12 forms into their blood, either sublingually or by injection, in order to force enough of them to diffuse directly into the cells to be used without further processing inside the cells.

    I should also note that if a person is particularly low in NADPH, I suspect that they will also have problems with glutathione and related substances, because they will not be able to reduce glutathione readily after it becomes oxidized. This will cause a buildup of oxidized glutathione and thus shift the redox potential in the oxidizing direction, worsening the oxidative stress and exacerbating all the associated symptoms. I suspect that this problem would show up more slowly than the problem I just described involving Cblc.

    So my point is that I believe that a given person who has ME/CFS may have one of these issues without having all of them, and as far as I can tell, most of the people don't have any of them. I'm basing this on the results of the clinical study that Dr. Nathan and I carried out, in which we used folic acid, folinic acid and hydroxocobalamin, and about two-thirds of the people had significant improvement. It is certainly possible that at least some of the other third had one or more of these problems, but there was also evidence that some had biotoxin illnesses, and this could have prevented their recovery as well.

    I'm glad that Freddd is attempting to get more information about how people are affected by these supplements. This could end up helping people who do not respond well to the simplified treatment protocol that I have suggested. If we can understand why, we might be able to do some relatively inexpensive genetic characterization, such as with www.23andme, and be able to determine what protocol would work best for different people.

    So I hope that people will try to distinguish which of these issues they actually have, and not assume that if they have one of them, they must have all of them.

    Best regards,

    Rich
    Lotus97, Hoops and Athene like this.
  13. Freddd

    Freddd Senior Member

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    Hi Rich,

    Thankyou for these explanations. They are helpful. The only tie in I have seen suggested is that if people can't do folinic acid they often have trouble with folic acid. However, I am trying to be able to distinguish each item separately , and that is tricky. The reason I suggest removing all of the potentially involved substances at once is to see if an induced folate deficiency exists for ANY of the reasons and then to work backwards with one item at a time. There do appaear to be some distinguishing features and that will show up in the first of multiple iterations of the questionaire. For those with veggie folate problems those are then exposed, but only by stopping all the others is it possible to realate it to food.

    I'm also working on a proto type spreadsheet data collection model. Any suggestion for any of these things you have I would like to hear. Data collection and analysis has been what I've done for decades when you get down to it. My "specialty" has been spotting patterns in the data and metadata. Give me the data on a million people and I can tell you a whole lot. In 1983 we completely changed how group medical programs were evaluated. Before that selected data from the insurance companies was handed over on paper in effect sampling a small percentage of the whole with filtered data from the insurance companies. When we changed to 100% of raw data, we found out how the insurance companies had been manilupating things. What made that possible was large enough hard disk and database systems on PCs with unlimited CPU time to analyze the data. Does anybody out there need a 9-track 10.5" reel tape machine for PCs? Its a faily compact item that weighs only 80 pounds or so and supports 800, 1600 and 3200 bpi.
    Athene likes this.
  14. dannybex

    dannybex Senior Member

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    Interesting list Athene. I had tried folinic for probably 2-3 weeks, just tiny amounts each day, but was also getting weaker, and twitchier.

    I'm assuming that your symptoms improved when you stopped the folinic? Are you taking just the methylfolate (and mb12?, etc) now?

    Thanks in advance,

    Dan
  15. Freddd

    Freddd Senior Member

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    Hi Anniekim,

    How do people determine they have folate deficiencies by stopping things such as nac, whey and taking metafolin?

    If a person is taking glutathione, NAC, Whey and a few other things known (like some drugs) and unknown (not yet identified), SOME people, percentage unknown, what distinguishes them unknown, will develop "detox" symptoms. These are identified all over the place as "detox" symptoms. The most severe ones also show up on Cerefolin-NAC package insert as the side effects. These side effects are not found for Deplin or Metanx. Metanx, Cerefolin and Deplin are pimarily Metafolin. Metanx and Cerefolin have some methylb12 and Metanx has p5p. The side effects of Cerefolin -NAC is a subset of those listed for glutathione and NAC "detox" at various places around the web.. When one site speaks of gastro intestinal ills, and another says nausea and dirrhea they are speaking of the same things even though they describe it differently. So one site may say "flu like symptoms and another may say body aches and mallaise and again it's the same thing.

    When there are these side effects from NAC and glutathione and these substances are stopped and Metafolin is substituted certain symptoms will go away very quickly. If the person is taking mb12/adb12 as well and having no effect from them and then when they stop the NAC - glutathione they have sudden startup in addition to the specific other symtoms falling off rapidly, they have an induced folate deficiency from the NAC - Glutathione.

    We are interested in hearing about all the various things and then deriving a list that come up over and over, maybe a quickly developing and slower developing list or who knows. Thats's why I'm asking this in a free form way right now. I don't know exactly what I'm looking for. I need people to tell me so I can try to combine the same symptoms by different descriptions and all the various things that show up. And if they can describe similar things from folic acid that clear up when the switch to Metafolin thats good too.

    I'm sure that this will go though a number of iterations. Also. when people see other posts they may get reminded of some they might have missed There might be 30 different symptoms but 5 that almost every body gets quickly and 5 in the longrun or who knows. So everything helps.Having the type of information transfer made possible by the internet we can do something like this in days that might have taken 10 years before.
    Lou and Athene like this.
  16. Athene

    Athene Never give up

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    Hi folks,

    Thanks for all that info Rich - my head is nearly exploding with that, as usual!
    Here's my biggest question, for Rich:
    Are these problems only caused by the genetic mutations you listed, or can the same situations be induced by infection? I have had CFS for 28 years now, I've been diagnosed with many infections (Lyme, bartonellla, chlamydia pneumonia among others) and I can swear the symptoms that we are talking about here have fluctuated considerably over the years - which they could not do if this were genetic, could they?
    I know that chlamydia pneumonia interferes with ATP production which leads to secondary porphyria. What role could that potentially play in creating this whole situation?


    Anyway, my NAC supply has just run out, so as of today I am not taking NAC. I'll report on what happens.

    Hi Dannybex, yes the symptoms wore off gradually over about 2 weeks once I stopped taking folinic acid. Did your symptoms wear off after you stopped Folinic acid?

    I am not taking methylfolate yet, not having any form of folate for now.

    I am taking whopping doses of B12 but my doctor wants to test my blood for the actual levels. He thinks there is something up with my needing so much and thinks we need to dig deeper. He said you can have other nutrients missing that can be masked by taking tons of B12, for example.
    Anyone know which specific test I ought to get for B12? Are there different types? My doc is very open minded and happy to order any test I ask him for.

    Thanks everyone for contributing to this very useful thread!
  17. Freddd

    Freddd Senior Member

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    Hi Athene,

    The NAC, if it affects you like me could completely wipe out any amount of b12. Taking the methylfolate might in effect ativate the mb12. Then make dose change.

    If a person is taking 1mg or so a day of active b12s, adb12/mb12, there is no meaningful test possible that I know of. Adjust doses after on methylfolate, no NAC, no glutathione. Add some adb12 if you are not taking it. Give yourself a chance to stabilize aftrer these things are changed. The one that might tell you that you have trouble getting cobalamin into you CSF/CNS is a spinal draw and measurement of cobalamin, hcy and mma in spinal fluid and find that you have low cobalamin as do people with CFS and FMS. There are no standards to interpret those.
  18. richvank

    richvank Senior Member

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    Hi, Athene.

    I think that the NADPH supply could drop in response to infection, and that could impact the ability to use folic acid as well as the ability to recycle glutathione. So yes, I think infection could come into the picture. During infection, the neutrophils and macrophages make reactive oxygen species in order to attack the enemy. This places a load on glutathione, which becomes oxidized and needs to be reduced by glutathione reductase, which makes use of NADPH.

    In ME/CFS, there appears to be a functional deficiency in B12, rather than an absolute deficiency. A blood serum B12 test will often show a normal or high B12 level in the blood, but most of this is B12 that has been exported by the cells and is bound to haptocorrin, which is eventually picked up by the liver and recycled back to the gut for possible reabsorption. The B12 in the blood that is bound to haptocorrin is not available to be used by the cells in general, but only to be recycled via the liver. The smaller fraction of B12 in the blood that is bound to transcobalamin is the part that can be imported by the cells of the body in general. The functional deficiency results from a problem within the cells that causes them not to be able to use B12 properly, so they export it back to the blood. In my hypothesis, this problem is glutathione depletion, which blocks the CblC complementation group. This seems to be the issue for most people who have ME/CFS. However, there are others, including Freddd, who appear to have an inherited mutation in this group or in another part of the intracellular B12 processing pathway.

    If the serum B12 level is normal or high, and the urine methylmalonate (as is included in urine organic acids tests or can be run as a separate test) is also high, that is good evidence for a functional B12 deficiency.

    Best regards,

    Rich
  19. Freddd

    Freddd Senior Member

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    Hi Rich,

    I would like to expand on that. The MMA will detect specifically a shortage of adb12 in the mitochondria. The HCY test applies specifically to mb12 and/or methylfoalte and/or p5p. However, "normal" "in-range" levels of MMA and HCY do not show sufficiency. And that is the problem. The tests won't tell you what a trial will. The trial is needed whether the tests are run or not. They are not definitive. Somewhere on one of the threads is a listing of all the problems of relying on the tests in peer reviewd articles. They are not predictive of non-reponse and those markers don't show up until the system is extremely broken. They can tell you that you are in BAAAAD trouble but not that you would benefit. "Normal" is based on a popualtion with 50% having at least some deficiency.
  20. SJB944

    SJB944 Senior Member

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    Sorry, HCY stands for?

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